Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease Through the Resolvin E1 and ChemR23 Axis.
calcification, physiologic
fatty acids, omega-3
heart valve diseases
inflammation
lipids
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
25 08 2020
25 08 2020
Historique:
pubmed:
9
6
2020
medline:
1
9
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in cardiovascular prevention have recently been demonstrated in a large randomized, controlled trial. In addition, n-3 PUFAs serve as the substrate for the synthesis of specialized proresolving mediators, which are known by their potent beneficial anti-inflammatory, proresolving, and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and specialized proresolving mediators on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived specialized proresolving mediators in relation to the development of AVS. Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in noncalcified regions compared with calcified regions. Liquid chromatography tandem mass spectrometry-based lipid mediator lipidomics identified that the n-3 PUFA-derived specialized proresolving mediator resolvin E1 was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe n-3 PUFA-derived resolvin E1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.
Sections du résumé
BACKGROUND
Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in cardiovascular prevention have recently been demonstrated in a large randomized, controlled trial. In addition, n-3 PUFAs serve as the substrate for the synthesis of specialized proresolving mediators, which are known by their potent beneficial anti-inflammatory, proresolving, and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and specialized proresolving mediators on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived specialized proresolving mediators in relation to the development of AVS.
METHODS
Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe
RESULTS
We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in noncalcified regions compared with calcified regions. Liquid chromatography tandem mass spectrometry-based lipid mediator lipidomics identified that the n-3 PUFA-derived specialized proresolving mediator resolvin E1 was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe
CONCLUSIONS
n-3 PUFA-derived resolvin E1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.
Identifiants
pubmed: 32506925
doi: 10.1161/CIRCULATIONAHA.119.041868
pmc: PMC7439935
doi:
Substances chimiques
CMKLR1 protein, human
0
CMKLR1 protein, mouse
0
Receptors, Chemokine
0
Eicosapentaenoic Acid
AAN7QOV9EA
5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
GND3JH08JA
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
776-789Références
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